Sterically Demanding Unsymmetrical Diaryl-λ(3)-iodanes for Electrophilic Pentafluorophenylation and an Approach to α-Pentafluorophenyl Carbonyl Compounds with an All-Carbon Stereocenter

Abstract

A sterically demanding unsymmetrical pentafluorophenyl-triisopropylphenyl-λ(3)-iodane was developed as an effective reagent for the electrophilic pentafluorophenylation of various β-keto esters and a β-keto amide. 17 examples of α-pentafluorophenylated 1,3-dicarbonyl compounds 3 having a quaternary carbon center are provided. The resulting compounds were nicely transformed into chiral α-pentafluorophenyl ketones with an all-carbon stereogenic center in high yields and high enantioselectivities using asymmetric organocatalysis (up to 98 % ee) or asymmetric metal catalysis (up to 82 % ee).

Keywords: asymmetric organocatalysis; diaryl-λ3-iodanes; electrophilic pentafluorophenylation; palladium.

Scheme 1

Electrophilic pentafluorophenylation by 1 and transformations to chiral α-pentafluorophenyl ketones having an all-carbon stereocenter.

Scheme 2

Reagents and conditions: a) Oxone, TFA/CHCl₃, RT, 2 h; b) TsOH⋅H₂O, CH₃CN, RT, 3 h (87 % over 2 steps); c) ArH, CF₃CH₂OH or TFA, RT, overnight.

Scheme 3

Palladium-catalyzed decarboxylation of β-keto esters 3 d and 3 o to α-pentafluorophenyl ketones 4 a and 4 b. Reagents and conditions: a) Pd₂(dba)₃ (2.5 mol %), dppe (6.25 mol %), Meldrums acid (2.5 equiv), THF, RT or 50 °C, 1–2 h.

Figure 1

X-ray crystallographic structure of (R)-5 e (CCDC 1009021).

Scheme 4

Creation of an all-carbon stereogenic center with C₆F₅: Palladium-catalyzed asymmetric decarboxylative allylation of 3 d and 3 o using the Trost ligand.